The objectives of this project are as follows: 1. Continue studies on islet cell secretion and islet cell replication using the perifusion system for long-term maintenance of islet cells in vitro, 2. Continue studies on tissue culture of isolated islets to remove passenger lymphocytes and macrophages prior to transplantation of islets as allografts, 3. Continue studies on the immunochemical localization of human pancreatic polypeptide in the dog and human pancreas, 4. Continue studies on the presence of perinuclear particles in the pancreas of juvenile diabetics and patients with idiopathic hypoglycemia. A perifusion system has been developed for the long-term maintenance of isolated rat islets in vitro. This system will be used to determine the effect of chronic maintenance of the islets with high and low concentrations of glucose on glucagon secretion and the effect of different insulin secretogogues on islet cell replication in this system. Studies on the removal of passenger lymphocytes and macrophages from isolated islets prior to allotransplantation is being attempted by prolonged tissue culture; utilization of anti-lymphocytes serum in vitro, as well as pretreating donor animals; utilization of silica in vitro and in vivo to destroy macrophages: and utilization of irradiation to deplete lymphocytes in donor animals prior to islet isolation. Studies will be continued on the immunochemical and ultrastructural localization of pancretic polypeptide in the canine and human pancreas. BIBLIOGRAPHIC REFERENCES: Lacy, P.E., Finke, E.H., Conant, S. and Naber, S: Long-term perifusion of isolated rat islet in vitro. Diabetes 25: 484-93, 1976. Wright, P.H., Gingerich, R.L., King, S. and Lacy, P.E.: Pancreatic lesions induced in rabbits and guinea pigs with pancreatic antigens. Clin. Exp. Immuno. 25: 328-337, 1976.